PDF(Pubmed)
Abstract：
Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN\'s activation of the NF-κB, Akt, p38, and PKA/CREB pathways.
摘要：
成纤维细胞生长因子21（FGF21）在代谢和脑功能中起着至关重要的作用。葡萄糖胺(GLN)因其不同的有益作用而被认可。本研究旨在阐明GLN对FGF21产生的调节及其对学习和记忆功能的影响。使用体内和体外模型，我们研究了GLN对正常饮食或高脂饮食小鼠和小鼠HT22海马细胞的影响，STHdhQ7/Q7纹状体细胞，和用GLN攻击的大鼠原代皮层神经元。我们的结果表明，GLN促进小鼠的学习和记忆功能，并上调海马中FGF21的表达，皮质,和纹状体,以及在HT22细胞中，STHdhQ7/Q7细胞，和皮质神经元。在接受GLN和FGF21受体FGFR1抑制剂（PD173074）的动物中，GLN增强的学习和记忆功能以及海马中FGF21产生的诱导显着减弱。在探索潜在分子机制的同时，NF-κB的潜在参与，Akt,p38,JNK,PKA,和PPARα在HT22和NF-κB中，Akt,注意到STHdhQ7/Q7中的p38和PPARα；GLN能够介导p65，Akt，p38，和CREB在HT22和p65，Akt，和p38在STHdhQ7/Q7细胞中。我们的累积发现表明，GLN可能通过诱导大脑中FGF21的产生来增加学习和记忆功能。这种诱导似乎是介导的，至少在某种程度上,通过GLN激活NF-κB，Akt,p38和PKA/CREB途径。
